Pharmacodynamic model of testosterone suppression after intramuscular depot estrogen therapy in prostate cancer

Johansson, Charlotta; Gunnarsson, Per Olov

doi:10.1002/1097-0045(20000615)44:1<26::aid-pros4>3.0.co;2-p

Cited by 2 publications

(1 citation statement)

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“…The serum concentrations of estradiol are governed by flip-flop pharmacokinetics and a limited rate of hydrolysis following im. injection, and the median rate of input was reported to be 0.21 days while the elimination output was 0.001 days -1 [116]. …”

Section: Drug Examplesmentioning

confidence: 99%

Flip-flop Pharmacokinetics – Delivering a Reversal of Disposition: Challenges and Opportunities During Drug Development

Yáñez

Remsberg

Sayre

et al. 2011

Therapeutic Delivery

203

108

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Flip-flop pharmacokinetics is a phenomenon often encountered with extravascularly administered drugs. Occurrence of flip-flop spans preclinical to human studies. The purpose of this article is to analyze both the pharmacokinetic interpretation errors and opportunities underlying the presence of flip-flop pharmacokinetics during drug development. Flip-flop occurs when the rate of absorption is slower than the rate of elimination. If it is not recognized, it can create difficulties in the acquisition and interpretation of pharmacokinetic parameters. When flip-flop is expected or discovered, a longer duration of sampling may be necessary in order to avoid overestimation of fraction of dose absorbed. Common culprits of flip-flop disposition are modified dosage formulations; however, formulation characteristics such as the drug chemical entities themselves or the incorporated excipients can also cause the phenomenon. Yet another contributing factor is the physiological makeup of the extravascular site of administration. In this article, these causes of flip-flop pharmacokinetics are discussed with incorporation of relevant examples and the implications for drug development outlined.

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Section: Drug Examplesmentioning

confidence: 99%